Wiley最新文献

The bud bank of perennial grasses is a key aspect of their reproduction and longevity in frequently burned ecosystems. We investigated how fire intensity and time since fire affected fire-stimulated flowering and bud activity of wiregrass (Aristida beyrichiana), a foundational bunchgrass in south-eastern US pine savannas. We manipulated fuels and monitored fire temperatures in plants during an experimental fire. We tested effects of plant size and fire intensity on flowering stem production and proportions of active and dead buds. We compared active, dead and total buds from plants in the experimental burn with those in stands burned one and 2 years ago, and described the species' bud morphology and anatomy. The duration above 60 °C had a marginally significant negative effect on the number of flowering stems per plant. This effect was less than the significant positive correlation of flowering stem number with plant size. Fire intensity did not affect the proportions of dead and active buds 5 months after fire. There were significant differences in proportions of active, dead and dormant buds 1 year after fire, and the total number of buds decreased with time since fire. Plants had an average of one bud per tiller, and mean bud depth was 3 cm. Perennial bud banks are a substantial source of regenerative biomass for plants in fire-prone savannas. For fire-stimulated flowering species, frequent fires are likely important for maintaining large bud banks that supply both vegetative and flowering structures. A focus on belowground structures should shed light on long-term ecosystem dynamics in fire-prone ecosystems.

Verekitug, a novel, high-affinity, fully human monoclonal antibody targeting thymic stromal lymphopoietin receptor (TSLPR), is in development as a potential treatment for severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD). This phase 1b, double-blind, randomized, placebo-controlled, multiple ascending-dose trial assessed the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of verekitug administered subcutaneously in patients with mild-moderate asthma. Thirty-two participants were randomized in 4 placebo-controlled dosing cohorts (3 × 100-mg or 200-mg doses, once every 4 weeks; 2 × 300-mg doses, once every 12 weeks; single 25-mg dose) and observed for 32 weeks. The primary endpoint was safety; secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints included TSLPR occupancy and biomarker effects. Treatment-emergent adverse events were mild or moderate. Complete TSLPR occupancy was observed at the first timepoint (2 weeks post dose) and maintained for 24 weeks (doses ≥100 mg). Rapid mean reductions in fractional exhaled nitric oxide, eosinophils, and interleukin-5 (up to -54%, -65%, and -64%, respectively) were sustained up to 24 weeks (doses ≥100 mg). The mean verekitug half-life was ~20 days. Low-titer antidrug antibody response was observed in some participants, without clinically meaningful impact on pharmacokinetics, pharmacodynamics, or safety. Verekitug was generally well tolerated, with rapid, substantial, and sustained effects on asthma biomarkers. These findings support further development of verekitug for treating severe asthma, CRSwNP, and COPD.

Plants are multicellular organisms composed of diverse cell types, each with its own distinct mRNA, protein and metabolite profile. In addition, each cell type exhibits developmental gradients that require fine-tuned balancing with neighbouring cells in terms of cell geometry and chromatin status. These factors highlight the need for precise knowledge of gene expression and chromatin dynamics during stress responses at the single-cell level in planta, linked to cell position and fate. In this viewpoint, we discuss the importance of spatial cell biology in situ methods in modern plant research and briefly compare it with the methods currently available for studying single-cell resolution.

Myocardial infarction triggers irreversible cardiomyocyte loss, sustained oxidative stress, and inadequate angiogenesis, often culminating in heart failure. Effective interventions must address these intertwined pathologies with spatiotemporal precision - a goal conventional antioxidants and regenerative strategies fail to achieve. Here, we develop a multifunctional single-atom nanozyme (SAzymes) platform featuring atomically dispersed Fe, Cu, or Mn centers on nitrogen-doped carbon (M-N-C) frameworks. This atomic-level design maximizes catalytic site utilization and broad-spectrum ROS scavenging, while exploiting the intrinsic bioactivity of trace metals. Systematic catalytic profiling identified Fe- Cu-, and Mn-SAzymes as optimal, each exhibiting complementary superoxide dismutase-, catalase-, and peroxidase-like activities. In hypoxia-challenged cardiomyocytes, these SAzymes not only eliminated ROS catalytically but also activated the NRF2/HO-1 endogenous antioxidant pathway, yielding synergistic redox regulation. In a rat MI model, intramyocardial SAzymes delivery preserved ventricular function, reduced infarct size, promoted angiogenesis, attenuated inflammation and fibrosis, and showed no systemic toxicity. Transcriptome analysis further revealed metal-specific therapeutic signatures - with Fe engaging PI3K-Akt/NF-κB, Cu activating AMPK/PPAR, and Mn modulating MAPK/TNF/NF-κB signaling - linking atomic metal identity to distinct biological repair programs. By uniting catalyst engineering with multi-omic mechanistic insight, this study positions trace-metal SAzymes as a versatile and tunable nanomedicine for ischemic heart disease and beyond.

Aims: Diabetic ketoacidosis (DKA) is a serious complication of diabetes, requiring intravenous (IV) insulin until resolution and subsequent transition to subcutaneous insulin. Currently, clinical guidelines vary regarding the timing of long-acting subcutaneous insulin initiation, with some advocating early administration during IV insulin infusion, while others recommend delaying until DKA resolution. We aimed to evaluate the efficacy and safety of concurrent versus sequential initiation of long-acting subcutaneous insulin in paediatric and adult patients with DKA already receiving regular insulin.

Materials and methods: A systematic search of five databases (inception to January 2026) identified eligible studies. Early initiation was defined as administration of long-acting insulin before resolution of DKA, while late initiation occurred after resolution of DKA. Primary outcomes included time to DKA resolution, total IV insulin and fluid requirements, and risks of hypoglycaemia, hypokalaemia, and rebound hyperglycaemia. Pooled effect sizes were calculated using random-effects models.

Results: Nine randomised control trials encompassing 652 patients were included. Early long-acting insulin was associated with a shorter time to DKA resolution (SMD: -0.61; 95% CI: -0.83 to -0.38) and was associated with lower total insulin and fluid requirements. Available evidence was insufficient to rule out an increased risk of hypoglycaemia (RR: 0.81; 95% CI: 0.52-1.27) or hypokalaemia (RR: 1.21; 95% CI: 0.90-1.63).

Conclusions: Early initiation of long-acting insulin during IV insulin infusion in DKA likely shortens time to resolution based on moderate certainty evidence and may reduce total insulin and fluid requirements. Evidence for rebound hyperglycaemia and recurrent DKA outcomes remains limited and imprecise.

Aims: Oxidised lipoproteins-including oxidised high-density lipoprotein cholesterol (ox-HDL-C), oxidised low-density lipoprotein cholesterol (ox-LDL-C) and oxidised lipoprotein(a) [ox-Lp(a)]-are emerging biomarkers of oxidative stress and vascular inflammation. However, their roles in glycometabolic disorders and the progression from prediabetes to type 2 diabetes mellitus (T2DM) remain poorly defined. To prospectively assess the associations between plasma ox-HDL-C, ox-LDL-C and ox-Lp(a) levels and the future risk of T2DM among individuals with prediabetes.

Materials and methods: This multi-centre, prospective cohort study enrolled 3056 participants, including 1521 individuals with prediabetes who were followed for 5 years. Baseline levels of ox-HDL-C, ox-LDL-C and ox-Lp(a) were quantified using ELISA. Glycaemic indices, insulin resistance markers and β-cell function were assessed. Associations with incident T2DM were evaluated using logistic regression, Cox proportional hazards models and restricted cubic spline analyses.

Results: Elevated baseline levels of ox-HDL-C, ox-LDL-C and ox-Lp(a) were independently associated with increased odds and hazard ratios for progression from prediabetes to T2DM. These associations were dose-dependent and remained significant across sex-specific subgroups. Additionally, oxidised lipoproteins correlated positively with FBG, HbA1c and HOMA-IR, and negatively with HOMA-β and HOMA-IS, suggesting a relationship with β-cell dysfunction and insulin resistance.

Conclusions: Ox-HDL-C, ox-LDL-C and ox-Lp(a) are independent, dose-dependent predictors of T2DM development in individuals with prediabetes. Their close association with impaired β-cell function highlights their potential utility in early risk stratification and targeted prevention strategies for T2DM.

Aims: To assess the effectiveness of behavioural economics-based financial incentive and social comparison feedback in adults with newly diagnosed type 2 diabetes.

Materials and methods: We conducted a pragmatic randomised control trial with 6-month intervention and 3-month post-intervention follow-up. Participants were randomised to three groups: financial incentive (FI), financial incentive and social comparison feedback (FS), and control. Intervention groups received loss-framed financial incentives to meet personalised weekly step-count targets, with the FS group additionally receiving peer encouragement. We performed intention-to-treat analysis with multiple imputation and generalised estimating equations (GEE).

Results: Among 99 adults newly diagnosed with type 2 diabetes, mean HbA1c at baseline in the control, FI, and FS groups were as follows: 52.5 (NSGP: 7%) (SD: 5.4), 52.9 (7%) (4.1), and 54.5 (7.1%) (4.9) mmol/mol. There were no significant decreases in HbA1c, weight, cholesterol or triglycerides in the incentive groups versus control at 6 or 9 months. There were significant increases in step count and physical activity at 6 months compared to control (FI: +1283 steps/day, p < 0.001; FS: +1545 steps/day, p < 0.001; FS group +774 MET-minutes/week, p < 0.001).

Conclusions: Financial incentive and social comparison feedback improved physical activity in people newly diagnosed with type 2 diabetes but were insufficient to achieve a significant improvement in glycaemic control.